The primary objective of this exploratory grant is to determine the value of consanguineous pedigrees for quantitative trait mapping and to perform initial gene mapping studies for selected quantitative traits that are significant risk factors for common ocular complex disorders such as glaucoma, and macular degeneration. A long-term goal is to use this approach to develop and support a genotype/phenotype database that will enable investigators to discover, assess and validate genes and biomarkers responsible for quantitative traits that contribute to complex human ocular disease. A major motivation for the project is the expectation that the resources obtained will provide new opportunities for the identification of significant risk factors for blinding human disease. In addition to phenotypic and genotypic data, environmental information will be collected to aid studies of gene environment interactions. DNA and plasma from blood samples collected from each study participant will be stored for future genomic, protein and small molecule analysis with the anticipation that this information will lead to the identification of genetic predictors and biomarkers for some complex ocular disorders. The underlying hypothesis of this proposal is that consanguineous pedigrees can provide more information for mapping genes responsible for quantitative traits than families without consanguineous relationships. Preliminary studies have suggested that consanguineous pedigrees of sufficient size and structure will provide more power for quantitative trait mapping than a similarly sized collection of nuclear families. The immediate goals of this pilot project are to use large consanguineous pedigrees for initial analyses to verify their usefulness for quantitative trait mapping, and to examine the inheritance of selected quantitative traits in inbred families. We plan to accomplish the following specific aims: 1) Identify and enroll members from large consanguineous pedigrees living in southern India, 2) Measure selected ocular quantitative traits for all participating individuals, 3) Collect peripheral blood samples on all available family members and prepare DNA and plasma samples, 4) Develop strategies for collecting environmental exposure information on all participating individuals, 5) Perform initial SNP genotyping, and 6) Perform initial mapping of quantitative trait loci. Common age-related disorders such as macular degeneration, glaucoma, cataract, and diabetic retinopathy, are the leading causes of blindness in many countries throughout the world, and with the aging of the population world-wide, the prevalence of these disorders is expected to increase dramatically by the year 2020. Age-related diseases are costly to treat, threaten the ability of older adults to live independently and in some countries increase the risk of mortality. The goal of this project is to identify genes responsible for ocular quantitative traits that are major risk factors for these common blinding disorders. The identification of these genes will help define the underlying causes of these disorders which will lead to new methods of treatment and diagnosis.